tbuckley/cabot-search huggingface dataset:
P11.15.A IMPACT OF PERIOPERATIVE DEXAMETHASONE IN THE CONTEXT OF NEUROSURGICAL BRAIN METASTASIS RESECTION
Authors: D Wasilewski, J Bukatz, R Peukert, Z Shaked, P Poeser, A Karbe, A Trelinska-Finger, C Jelgersma, A Frueh, M Raspe, H Radbruch, D Capper, M Schlaak, P Thuss-Patience, P Bischoff, D Horst, M Krentzke, R Xu, F Ehret, D Kaul, M Misch, L Bullinger, N Frost, P Vajkoczy, J Onken
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Patients with brain metastases that undergo brain metastasis resection regularly receive perioperative dexamethasone. We sought to evaluate whether perioperative dexamethasone in brain metastases is linked to survival. MATERIAL AND METHODS Retrospective data on perioperative dexamethasone dosage in resected brain metastasis patients at three hospital sites of the Charité from 2010-2022 were collected. Cut-off values for cumulative perioperative dexamethasone dose as a continuous predictor variable for survival were determined using maximally selected rank statistics. Patients were dichotomized based on determined cut-offs of cumulative dexamethasone (pre-operative: &amp;lt; 40 mg vs ≥ 40 mg; post-operative: &amp;lt; 180 mg vs ≥ 180 mg) and pre- and postoperative: &amp;lt; 281 mg vs ≥ 281 mg). Medical records included baseline demographic, radiological, histopathological and treatment-related characteristics. Based on cut-off values for dexamethasone downstream statistical analyses included Kaplan-Meier, Cox proportional hazards regression for overall survival with adjustment for potential confounders including age, gender, Karnofsky performance index and presence of extracranial metastasis via propensity score matching. RESULTS 539 patients were included. Median follow-up time was 58,97 months. After adjusting for age, gender, Karnofsky performance index and presence of extracranial metastasis patients with higher cumulative perioperative dexamethasone (≥281 mg) showed shorter survival (HR: 1.47 (1.20-1.80, p&amp;lt;0.001) as compared to patients with lower cumulative doses (&amp;lt;281 mg). This effect remained significant after correction for patients that died within 3 months after resection and for patients with KPS below 50% and, independently from this approach performing propensity score matched-based analysis of the total cohort of patients, respectively. CONCLUSION Cumulative perioperative dexamethasone is associated with decreased survival in the context of brain metastasis resection. Strict dosage, down taper or methods reducing corticosteroid dependency should be regularly evaluated in clinical practice in patients with brain metastases
P16.06.A INCIDENCE, FOLLOW UP AND OUTCOME IN INCIDENTAL MENINGIOMA IN THE GOTHENBURG REGION - WHAT HAS HAPPENED IN 10 YEARS?
Authors: O Näslund, P S Strand, O Solheim, M Al Masri, O Rapi, E Thurin, A S Jakola
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Meningiomas constitute a large portion of brain tumors, with an often indolent natural course of disease. There a now more asymptomatic meningiomas diagnosed each year as compared to their symptomatic counterparts. With brain imaging widely available, increased findings of incidental meningiomas have emerged. There are many unique challenges to the management of incidental meningioma, where if no symptoms are present, there is a lack of evidence-based guidelines for follow-up and treatment. The aim of this study was to map the use of brain scanning, and the subsequent findings of presumed incidental meningioma between the years 2008-2009 and 2018-2019, and to study differences in follow-up, treatment, and outcome among these patients. MATERIAL AND METHODS Records of performed CT and MRI of the brain at the radiological departments at three hospital sites were retrospectively reviewed in search for patients with presumed incidental meningioma. Their medical health records were the used to study the natural course and clinical handling of these patients. RESULTS An almost identical number of patients underwent brain scanning at our three hospital sites during the two time periods (n=22 259 vs. 22 013). In 2018-2019, 25% more incidental meningiomas were diagnosed as compared to 2008-2009 (n=161 vs. 129). In the later years, patients had a higher median age (79 years vs. 73 years, p=0.03) and more often underwent brain imaging due to non-metastatic cancer (n=38 vs. 15, p=0.009). There were no differences in the indication for diagnostic scanning, nor management decision at time of diagnosis. CONCLUSION We could not show an increase in patients undergoing scanning of the brain between the two time periods studied, but with passing time it has become more common to frequently scan the brain of elder individuals, and individuals with cancer without metastases, perhaps due to improved treatment options for patients if metastatic disease was found. When an incidental meningioma was subsequently found, no differences could be seen in the clinical handling of the patients in terms of treatment or follow-up.
P11.62.A GENDER-RELATED DIFFERENCES IN PATIENTS CHARACTERISTICS, AND TREATMENT OUTCOME IN A COMPARATIVE STUDY OF MICROSURGERY AND RADIOSURGERY OF VESTIBULAR SCHWANNOMA
Authors: S Wang, K Machetanz, A van Eck, G Horstmann, M Tatagiba, G Naros
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Gender-related differences in patients with sporadic, unilateral vestibular schwannoma (VS) are poorly investigated so far. In studies focusing on natural history, tumor growth was described to be indifferent in either sex. However, it remains unclear whether patient’s sex affects the treatment response to stereotactic radiosurgery (SRS) or microsurgical resection (SURGERY). This study elucidates sex-related differences in VS care. MATERIAL AND METHODS This is a retrospective multi-center cohort study. Data was retrospectively collected from two large centers involved in the treatment of vestibular schwannomas for patients between 2005 und 2011 to enable long-term follow-up (FU). Tumor size was classified by Koos Classification. Previously treated VS and patients with Neurofibromatosis were excluded. Clinical state was reported by House and Brackmann (H&amp;B) and Gardner-Robertson (G&amp;R) scale (with H&amp;B&amp;lt;3 and G&amp;R 1-2 considered as good outcome), and Recurrence-free-survival (RFS) was assessed radiographically by contrast-enhanced MR imaging. Data on VS-associated symptoms like trigeminal affection, tinnitus, and vertigo/imbalance were also collected. RESULTS The study population included N=901 patients, who were treated in both centers. N=502 (56%) VS patients were female and N=399 (44%) were male. At time of treatment, women (56 years SD±13.50) were significantly older in age then men (53 years SD±13.80) (p=0.001). Tumor size, cystic morphology, intracanalicular extension, provided care (SRS, SURGERY), treatment related complications, and extent of surgical resection were insignificant in both gender-groups. The incidence of relevant preoperative vertigo was higher in women (67%) then in men (55%) (p=0.002). Pre- and postoperative facial function, hearing loss, and trigeminal symptoms were similar in both groups. Overall incidence of recurrence was insignificant (p=0.106). However, the in subgroups, tumor control with SRS was significantly worse in women compared to men (p=0.035). CONCLUSION Provided Care, functional outcome and peri-interventional morbidity were the same in either sex. Relevant vertigo was significantly more often present in women. The incidence of recurrence is higher in women with VS, when treated with SRS compared to men, although tumor characteristics were similar. Additional research is needed to elucidate gender-related difference in tumor biology affecting the response to VS treatment.
JS09.7.A COMBINATION OF APPARENT DIFFUSION COEFFICIENT AND FET PET COMPARED WITH STANDARD IMAGING FOR QUANTITATIVE TUMOR PRESENCE IN DIFFUSE GLIOMAS
Authors: K Tjong Tjin Joe, P Wesseling, F Barkhof, J Beliën, M M Yaqub, P J W Pouwels, R Verhaak, J C Reijneveld, A J M Rozemuller, W P Vandertop, R Boellaard, F Barthel, P C de Witt Hamer, E van de Giessen, N Verburg
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Diffuse glioma local treatment is currently guided by standard MRI sequences. Yet, the combination of apparent diffusion coefficient (ADC) and O-(2-[18F]-fluoroethyl)-L-tyrosine positron emission tomography (FET PET) (ADC/FET) detects histopathological qualitative assessed tumor presence more accurately than standard imaging. It is unknown whether this is similar for quantitative assessed tumor presence. This study compares the diagnostic accuracy of standard imaging and ADC/FET for the detection of quantitative assessed tumor presence in diffuse glioma. MATERIAL AND METHODS Fifteen patients with newly diagnosed diffuse glioma were retrospectively included. Pre-operative standard imaging, ADC and FET PET were available. Multiregional image-guided stereotactic biopsies were acquired before craniotomy. Quantitative imaging data from regions-of-interests (ROIs) centered at the biopsy locations was obtained. For each biopsy, sample semi-automatic cellularity and proliferation index, as well as DNA methylation-based tumor purity was determined. Linear mixed models were used to evaluate which modalities were significant independent predictors for each tumor presence marker and fitness was assessed using Bayesian Information Criterium. RESULTS 125 biopsies were analyzed (75 from eight high grade and 50 from seven low grade gliomas). Cellularity was predicted by T1 weighted MRI (p = 0.033), ADC (p = 0.016) and ADC/FET (p &amp;lt;.001), with ADC/FET as best fit. Both proliferation index (p = 0.003) and tumor purity (p &amp;lt;.001) were only predicted by ADC/FET. CONCLUSION Combining ADC and FET PET predicts cellularity, proliferation index and tumor purity better than standard imaging. Further investigation into ADC/FET-guided local treatment of diffuse glioma is therefore needed.
P11.09.A SIGNIFICANCE OF MOLECULAR DIAGNOSTICS FOR THERAPEUTIC DECISION MAKING IN RECURRENT GLIOMA
Authors: J Blobner, L Dengler, S Blobner, C Eberle, J Weller, N Teske, P Karschnia, K Rühlmann, K Heinrich, F Ziemann, P A Greif, I Jeremias, R Wuerstlein, K Hasselmann, M Dorostkar, P N Harter, S Quach, V Stoecklein, N L Albert, M Niyazi, J Tonn, N Thon, B C Westphalen, L Baumgarten
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Targeted therapies have substantially improved survival in cancer patients with malignancies outside the brain. Whether in-depth analysis for molecular alterations may also offer therapeutic avenues in primary brain tumors remains unclear. We herein present our institutional experience for glioma patients discussed in our interdisciplinary Molecular Tumor Board (MTB) implemented at the Comprehensive Cancer Center Munich (LMU). MATERIAL AND METHODS We retrospectively searched the database of the MTB for all recurrent glioma patients after previous therapy. Recommendations were based uponnext-generation sequencing results of individual patient’s tumor tissue. Clinical and molecular information, previous therapy regimens and outcome parameters were collected. RESULTS Overall, 73 consecutive recurrent glioma patients were identified. In the median, advanced molecular testing was initiated with the third tumor recurrence. The median turnaround time between initiation of molecular profiling and MTB case discussion was 48 ± 75 days (range: 32 - 536 days). Targetable mutations were found for 50 recurrent glioma patients (68.5%). IDH1 mutation (27/73; 37%), EGFR amplification (19/73; 26%) and NF1 mutation (8/73; 11%) were the most detected alterations and a molecular-based treatment recommendation could be made for all of them. Therapeutic recommendations were implemented in 12 cases (24%) and one third of these heavily pretreated patients experienced clinical benefit with at least partial response or disease stabilization. CONCLUSION In-depth molecular analysis of tumor tissue may guide targeted therapy also in brain tumor patients and considerable anti-tumor effects might be observed in selected cases. However, future studies to corroborate our results are needed.
OS06.7.A SOMATOSTATIN RECEPTOR SUBTYPE EXPRESSION AND RADIOMICS FROM DWI-MRI REPRESENT STANDARDIZED UPTAKE VALUES (SUV) OF68GA-DOTATOC PET IN PATIENTS WITH MENINGIOMA, A TRANSLATIONAL STUDY
Authors: S Iglseder, A Iglseder, V Beliveau, J Heugenhauser, E Gizewski, J Kerschbaumer, G Stockhammer, C Uprimny, I Virgolini, J Dudas, M Nevinny-Stickel, M Nowosielski, C Scherfler
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND In this translational study, we first aimed to analyse the expression of somatostatin receptor subtype (SSTR) 2A, 2B and 5 and their correlation with the maximum standardized uptake value (SUVmax) of 68Gallium DOTA-D-Phe1-Tyr3-octreotide Positron Emission Tomography (68Ga-DOTATOC PET) in patients with meningioma. Secondly, we aimed to develop a radiomic model based on apparent diffusion coefficient (ADC) maps derived from diffusion weighted magnetic resonance images (DWI MRI) to reproduce SUVmax. MATERIAL AND METHODS A total of 51 patients who underwent MRI and 68Ga-DOTATOC PET prior to surgical resection of intracranial meningioma were included in the imaging part of the study. SUVmax were quantified from the PET images. Segmentation of the post-contrast T1-weighted (cT1) MR images served as regions of interest and were mapped to the co-registered ADC maps. A total of 1940 radiomic features were quantified from the tumor area for each ADC map. A random forest regression model was trained to reproduce SUVmax values. The model was evaluated within a repeated nested cross-validation design. The training included a feature selection was done in two-steps using a minimum redundancy maximum relevance feature selection and a recursive feature elimination based. The expression of SSTR subtypes 2A, 2B and 5 was quantified in 18 surgical specimen of meningioma and compared to SUVmax values. RESULTS The SUVmax values predicted by the random forest models correlated significantly with the observed values (p &amp;lt; 0.05) for all 100 repeats with a mean Pearson’s r = 0.42 ± 0.07 SD and a RMSE = 28.46 ± 0.16. The expression of SSTR subtypes 2A, 2B and 5 correlated significantly with the SUVmax values (p&amp;lt;0.001, R2=0.669; p=0.001, R2=0.393; and p=0.012, R2=0.235, respectively). CONCLUSION In this translational study, SSTR subtypes 2A, 2B and 5 correlate significantly with SUVmax. We developed a random forest regression model using radiomic features to reproduce SUVmax from 68Ga-DOTATOC PET in meningiomas.
P11.02.B DO GENOMIC ALTERATIONS INFLUENCE THE DEVELOPMENT OF BRAIN METASTASES IN ADVANCED AND METASTATIC NON-SMALL CELL LUNG CANCER?
Authors: C S Gillespie, M A Mustafa, G E Richardson, A M Alam, K S Lee, D M Hughes, C Escriu, R Zakaria
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Lung cancer is the most common cause of cancer deaths worldwide. Development of brain metastases (BM) in patients with advanced (Stage III) and metastatic (Stage IV) non-small cell lung cancer (NSCLC) is linked with poor prognosis. Identifying mutations associated with BM development could influence screening and determine targeted treatment paradigms. We aimed to establish BM prevalence and incidence in patients with advanced and metastatic NSCLC, stratified by genomic alterations. MATERIAL AND METHODS A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO ID CRD42022315915). Three databases were searched, and articles published between January 2000-May 2022 included (Search date 30th April 2022). Prevalence at diagnosis, and incidence of new BM per year were obtained, including patients with EGFR, ALK, KRAS, ROS1, RET, MET, and other genomic alterations. Pooled incidence rates were calculated using random effects models. RESULTS Of 960 articles identified, 65 were included in the study (24,784 patients). Pooled BM prevalence at diagnosis was 28.6% (45 studies, 95% Confidence Interval [CI] 26.1-31.0), and highest in patients with ALK (34.9%) and RET translocations (32.2%). With a median follow-up of 24 months, the per-year incidence of new BM was 12.5% in the wild-type group (14 studies, 95% CI 10.9-15.9). Incidence in the subgroups with different genomic alterations was 15.6% in the EGFR group (16 studies, 95% CI 11.4-21.2), 17.0% in the ALK group (6 studies, 95% CI 11.3-25.8), 9.8% in the KRAS group (4 studies, 95% CI 5.5-17.5), 12.5% in the ROS1 group (3 studies, 95% CI 5.7-27.6), and 11.8% in the RET group (2 studies, 95% CI 8.0-17.5). At the end of the follow-up period, a median of 55.0% of patients had BM (IQR 44.2-67.8). CONCLUSION This is the first study to show prevalence, and incidence of BM development in advanced and metastatic NSCLC, stratified by genomic alterations. Our data indicates a higher prevalence and incidence of BM in patients with targetable genomic alterations. This supports brain imaging at staging and follow-up, underlining the need for NSCLC therapies with brain penetrance and efficacy.
P13.05.B INCORPORATION OF AI-BASED AUTOSEGMENTATION AND CLASSIFICATION INTO NEURORADIOLOGY WORKFLOW: PACS-BASED AI TO BUILD YALE GLIOMA DATASET
Authors: N Tillmanns, J Lost, S Merkaj, M von Reppert, S Chadha, M Lin, K Bousabarah, A Huttner, S Aneja, A Avesta, A Omuro, M Aboian
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Translation of AI algorithms into clinical practice is significantly limited by lack of large individual hospital-based datasets with expert annotations. Current methods for generation of annotated imaging data are significantly limited due to inefficient imaging data transfer, complicated annotation software, and time required for experts to generate ground truth information. We incorporated AI tools for auto-segmentation of gliomas into PACS that is used at our institution for reading clinical studies and developed a workflow for annotation of images and development of volumetric segmentations in neuroradiology clinical workflow. MATERIAL AND METHODS 1990 patients from Yale Radiation Oncology Registry (2012-2019) were screened. Segmentations were performed using a UNETR algorithm trained on BRaTS 2021 and an internal dataset of manually segmented tumors. AI generated segmentation can be revised and confirmed in PACS. Segmentations were validated by a board-certified neuro-radiologist, after which natively embedded PyRadiomics in PACS was used for direct feature extraction. RESULTS In 7 Months (05/2021 - 08/2021, 03/2022 - 05/2022) segmentations and annotations were performed in 1033 patients (429 female, 604 male, mean age 53 yrs). Dataset includes 595 Grade 4 Gliomas (96 Grade 3, 105 Grade 2, 45 Grade 1, 192 unknown). Molecular subtypes include IDH (129 mutated, 651 wildtype, 253 unknown), 1p/19q (94 deleted or co-deleted, 135 intact, 804 unknown), MGMT promotor (216 methylated, 110 partially methylated, 321 unmethylated, 383 unknown), EGFR (125 amplified, 248 not amplified, 660 unknown), ATRX (41 mutated, 238 retained, 754 unknown), Ki-67 (726 known, 307 unknown) and p53 (639 known, 394 unknown). Classification of gliomas between grade 3/4 and grade 1/2, yielded AUC of 0.85. CONCLUSION We developed a method for incorporation of volumetric segmentation, feature extraction, and classification that is easily incorporated into neuroradiology workflow. These tools allowed us to annotate over 100 gliomas per month, thus establishing a proof of concept for rapid development of annotated imaging database for AI applications.
P10.16.B ATR INHIBITION ENHANCES CELL DEATH AND INDUCES IMMUNE-RELATED GENE EXPRESSION IN COMBINATION WITH STANDARD TREATMENT IN PATIENT-DERIVED GLIOBLASTOMA CELLS
Authors: M Lozinski, N Bowden, M Graves, M Fay, B Day, B Stringer, P Tooney
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Patients with glioblastoma are confronted with a high likelihood of recurrence and poor prognosis despite an aggressive treatment-regime involving surgery followed by radiation therapy (RT) and temozolomide (TMZ). RT and TMZ cause extensive DNA damage and replication stress, thus activating tumour cell death pathways. Upregulation of the DNA repair mechanisms significantly reduces effective treatment response and contributes to poor patient outcomes. We investigated the effect of inhibiting ATM- and Rad3-Related protein (ATR), a crucial sensor of replication stress and initiator of cell cycle arrest in tumour cells, using the potent and selective ATR inhibitor, gartisertib. MATERIAL AND METHODS Twelve patient-derived glioblastoma cell lines were grown as monolayer cultures in serum-free media and treated with TMZ, RT and/or gartisertib. Cell viability of treated cells was assessed after a 7-day incubation using the MTT method, while cell confluence, apoptosis and cell death were examined using the Incucyte S3 Live-Cell Analysis System (Sartorius, Germany). Gene expression of glioblastoma cell lines treated with TMZ+RT and/or gartisertib was assessed 4-days post-treatment. RESULTS As a single agent, gartisertib potently reduced glioblastoma cell viability, while 8-fold less potent in human astrocyte cells. Glioblastoma cell lines with mutated DNA damage response-related genes were more sensitive to gartisertib treatment. Live-cell imaging of glioblastoma cells treated with gartisertib (1 µM) plus TMZ (35µM) and RT (2Gy) showed a significant increase in cell death and apoptosis compared to gartisertib or TMZ+RT alone. ATR inhibition by gartisertib strongly synergised with TMZ, while moderately synergising with RT in reducing glioblastoma cell growth. Gartisertib, alone and in combination with TMZ+RT, increased gene expression in pro-inflammatory cytokines, antigen presentation, and pattern recognition pathways while decreasing genes involved in hypoxia and epithelial-mesenchymal transition pathways. CONCLUSION These data suggest the potential for ATR inhibition as an effective chemo- and radiosensitiser in glioblastoma tumours. Whether the change in gene expression induced by ATR inhibition reduces hypoxia within or provokes an immunogenic response directed at glioblastoma tumours, requires further investigation.